Shioi Ko-ichi, Komiya Atsushi, Hattori Keiko, Huang Ying, Sano Futoshi, Murakami Takayuki, Nakaigawa Noboru, Kishida Takeshi, Kubota Yoshinobu, Nagashima Yoji, Yao Masahiro
Department of Urology and Molecular Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Clin Cancer Res. 2006 Dec 15;12(24):7339-46. doi: 10.1158/1078-0432.CCR-06-1737.
Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions. We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC).
We used real-time quantitative PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas, and 7 collecting duct carcinomas. We retrospectively examined the relationship of this expression to various clinicopathologic variables and the von Hippel-Lindau alteration status. We evaluated its significance with respect to patient survival rates using the Cox regression model combined with the split-sample method.
Compared with normal kidney samples (n = 43), VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in patients asymptomatic at presentation and in patients with small tumor size, low-stage, low-grade, microvascular invasion-negative, and von Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is significant only in cancer-free survival for patients with clear cell RCC after curative surgical resection.
VCAM1 expression levels were found to be histologically subtype specific in renal tumors. Determination of the VCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC.
血管细胞黏附分子1(VCAM1)是一种涉及多种病理生理状况的细胞表面糖蛋白。我们测量了肿瘤组织中VCAM1的表达水平,并评估了其在肾细胞癌(RCC)中的意义及预后价值。
我们使用实时定量PCR检测了总共485例散发性肾肿瘤的VCAM1表达水平,其中包括429例透明细胞癌、21例乳头状癌、17例嫌色细胞癌、11例嗜酸细胞瘤和7例集合管癌。我们回顾性研究了该表达与各种临床病理变量及von Hippel-Lindau改变状态之间的关系。我们使用Cox回归模型结合分割样本法评估了其对患者生存率的意义。
与正常肾样本(n = 43)相比,VCAM1在透明细胞RCC和乳头状RCC中显著上调,而在嫌色细胞RCC和嗜酸细胞瘤中下调。在透明细胞RCC中,VCAM1表达水平在初诊时无症状的患者以及肿瘤体积小、分期低、分级低、无微血管侵犯且von Hippel-Lindau改变阳性的肿瘤患者中明显较高。单因素分析表明,VCAM1高表达与透明细胞和乳头状RCC的更好预后密切相关。此外,Cox多因素分析模型结合分割样本法显示,这种关联仅在根治性手术切除后透明细胞RCC患者的无癌生存中具有统计学意义。
发现VCAM1表达水平在肾肿瘤中具有组织学亚型特异性。将VCAM1表达水平作为生物标志物进行测定可为透明细胞RCC患者提供有用的预后信息。